The Insight Segmentation and Registration Toolkit (ITK) is a highly utilized open source medical imaging library. Written in C++, ITK provides chiefly the functionality to register, segment, and filter medical images. Although extremely powerful, ITK has a very steep learning curve for users with little or no background in programming. It was for this reason that SimITK was developed. SimITK wraps ITK into the model driven engineering environment Simulink, a part of the Matlab development suite. The first released version of SimITK was a proof of concept, and demonstrated that ITK could be wrapped successfully in Simulink. Very few segmentation and registration functions were available and the system was based on ITK version 3 with a semi-automatic wrapping procedure. In this thesis a new version of SimITK is presented that includes thirty-seven image filter, twelve optimizer, and nineteen transform classes from ITK version 4 which are successfully wrapped and tested. These classes were chosen to represent a broad range of usability (in the case of the filters) and to allow for greater flexibility when creating registration pipelines by having more options for optimizers, transforms, and metrics. Many usability improvements were also implemented for the registration pipeline, including providing the user with the metric value while executing a registration model and allowing the output image size to be specified for certain filters. In order for SimITK to transition to a usable research tool, several usability improvements were needed. These included transitioning from wrapping ITK version 3 to ITK version 4, fully automating the wrapping process, and usability modifications to the registration pipeline including a metric value output. These implementations of an automated wrapping procedure for ITK version 4, and improved usability of the registration pipeline have propelled SimITK on a path towards a usable research tool. The author will be creating a release of these changes, updating installation documentation, and updating tutorials which are available at www.SimITKVTK.com / Thesis (Master, Computing) -- Queen's University, 2013-08-05 10:15:16.607

Background SMEs are the backbone of the economies across the world, and the different markets they function in have been globalized in recent years. This has resulted even greater demands on SMEs different capabilities to give them the competitive edge they need to stay in front of competition. Some identified capabilities that can give them superior advantage to competition are information technology, business process management and customer relationship management. These capabilities have been studied in different context and on different levels. However, in this study the focus is on the different dimensions of IT and CRM in relation to BPM. More specifically the dimension of IT being IT knowledge and IT operations and the dimension of CRM being Customer interaction management. Objectives The goals of this study are to give further understanding into the characteristics of the SMEs IT knowledge, IT operations, Customer interaction management and Business process management. And the interrelationship between these capabilities. Methods Structural equation modelling was used for the analysis of the answers received on a questionnaire sent out to different SMEs performing in different sectors on the Swedish market. Results The study resulted in 195 gathered answers, whereof 169 were used, from SMEs working in 9 different sectors, the predominant sector was the manufacturing sector. The results suggest that the CIM capabilities is the strongest one, followed up by ITK, BPM and the lowest being ITO. The analysis suggested rejected the hypothesis of a positive direct impact between ITK and CIM and ITO and CIM. But it accepted the hypothesis of a positive direct impact of BPM on CIM. Conclusions The findings suggest that SMEs must rethink their BPM and ITK capabilities as negative correlations were found between ITK and BPM. Additionally, it was found that BPM mediated a negative effect between ITK and CIM. Future research should be done to understand where the misfits between BPM and IT lies in SMEs in different sectors.

The semiconductor detectors of ATLAS experiment at CERN are exposed to high radiation for a long time, which reduces their efficiency. They need to be replaced and, if necessary, modernized. Nowadays, the entire Large Hadron Collider is planned to improve. Its luminosity will increase. During this shut- down, the detectors of ATLAS experiment will also be upgraded. This thesis is focused on strip detectors of a new inner detector of ATLAS experiment called ITk. For the correct interpretation of the measured results, it is important to know the detector's response. Test of detector response is, therefore, an important part of the process of developing. In this thesis, we focused on detectors' edges, where we assumed a different shape of the electric field, which may cause a different response. We chose the laser test because it is a position-sensitive measurement. 1

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<p>Denna rapport tar upp teorier och metoder kring användbarhet i skapandet av en Flash-applikation. Rapporten beskriver steg för steg i skapandeprocessen, hela vägen från att ta fram behov och användningsområde till att skapa innehållet och slutligen en utförlig redogörelse för hur applikationen sammansätts. Metoderna som använts är huvudsakligen ITK (Identity Tool Kit) och scenarier enligt Alan Cooper. Vidare har metoder för hopsättning och visualisering av applikationen använts med stöd av Nielsen och Raskins användbarhetsprinciper. Resultatet visar att för att använda ITK i syfte att kartlägga en verksamhet, kräver detta en stor förståelse och modifikation av denna. Det visar också att Alan Coopers teorier om scenarier inte heller kommer till sin rätt utan en utförlig analys av användarna i denna. Resultatet visar även att med hjälp av programvarorna 3D studio Max och Flash kan interaktivt innehåll för produktvisualisering på nätet skapas med goda resultat.</p> / <p>This report addresses the theories and methods of usability in creating a Flash application. The report describes step by step in the creative process, all the way from the development needs and use to create content and finally a detailed explanation of how the application assemblies. The methods used are mainly ITK (Identity Tool Kit) and scenarios according to Alan Cooper. Furthermore, methods of assembly and visualization of application used with the support of Nielsen and Raskin usability principles. The result shows that the use of ITK in order to identify an activity, this requires a great understanding and modification of this. It also shows that Alan Cooper's theories about the scenarios do not come into its own, without a detailed analysis of the users thereof. The results also show that using the software 3D Studio Max and Flash for interactive content for product visualization on the web is created with good results.</p>

Denna rapport tar upp teorier och metoder kring användbarhet i skapandet av en Flash-applikation. Rapporten beskriver steg för steg i skapandeprocessen, hela vägen från att ta fram behov och användningsområde till att skapa innehållet och slutligen en utförlig redogörelse för hur applikationen sammansätts. Metoderna som använts är huvudsakligen ITK (Identity Tool Kit) och scenarier enligt Alan Cooper. Vidare har metoder för hopsättning och visualisering av applikationen använts med stöd av Nielsen och Raskins användbarhetsprinciper. Resultatet visar att för att använda ITK i syfte att kartlägga en verksamhet, kräver detta en stor förståelse och modifikation av denna. Det visar också att Alan Coopers teorier om scenarier inte heller kommer till sin rätt utan en utförlig analys av användarna i denna. Resultatet visar även att med hjälp av programvarorna 3D studio Max och Flash kan interaktivt innehåll för produktvisualisering på nätet skapas med goda resultat. / This report addresses the theories and methods of usability in creating a Flash application. The report describes step by step in the creative process, all the way from the development needs and use to create content and finally a detailed explanation of how the application assemblies. The methods used are mainly ITK (Identity Tool Kit) and scenarios according to Alan Cooper. Furthermore, methods of assembly and visualization of application used with the support of Nielsen and Raskin usability principles. The result shows that the use of ITK in order to identify an activity, this requires a great understanding and modification of this. It also shows that Alan Cooper's theories about the scenarios do not come into its own, without a detailed analysis of the users thereof. The results also show that using the software 3D Studio Max and Flash for interactive content for product visualization on the web is created with good results.

Les lymphocytes T sont caractérisés par l’expression d’un récepteur à l’antigène des cellules T (TCR), soit le preTCR, soit le γδ TCR et le αβ TCR clonotypique, associé à un complexe de transduction formé du CD3 et de la chaîne ζ. La signalisation du complexe TCR:CD3:ζ est cruciale pour le développement des cellules T et pour leur activation spécifique par l'antigène. Ces signaux déclenchent la prolifération, la différentation, les fonctions effectrices et l’apoptose des cellules T. Les évènements proximaux de la signalisation du TCR:CD3:ζ impliquent des protéines tyrosine kinases (PTK) des familles CSK, SRC, SYK et TEC dont les acteurs principaux sont CSK (C-terminal SRC kinase), LCK (lymphocyte-specific protein tyrosine kinase), ZAP-70 (ζ chain-associated protein tyrosine kinase of 70 kDa) et ITK (interleukin-2-inducible T cell kinase). Après stimulation du complexe TCR:CD3:ζ, les PTKs sont activées et déclenchent une cascade de phosphorylation sur tyrosine dont la phosphorylation des motifs activateurs ITAM (immunoreceptor tyrosine-based activation motif) du CD3 et de la chaîne ζ, et la phosphorylation des protéines adaptrices. Celles-ci conduisent à l’assemblage du signalosome LAT:SLP-76, lequel contrôle en grande partie la diversité des signaux associés au complex TCR:CD3:ζ, dont le flux calcique, l’activation de la cascade des MAP kinases, l’activation des facteurs de transcription NF-κB, NFAT et AP-1 ainsi que la réorganisation du cytosquellette d’actine, l’adhésion cellulaire et la motilité. Pendant les cinq dernières décennies, le système immunitaire a été analysé extensivement in vitro et à l’aide de modèles animaux comme la souris. Par ailleurs, l’étude des déficits immunitaires héréditaires chez l’homme a permis aussi des avancées importantes et novatrices dans la compréhension du système immunitaire humain que les modèles animaux ne permettaient pas d’appréhender. Dans ma thèse de doctorat je rapporte le premier cas de déficit humain en LCK de transmission autosomique récessive et l’identification de nouvelles mutations autosomiques récessives provoquant un défaut humain de ZAP-70 et un défaut humain d’ITK. Je rends compte des phénotypes cliniques et immunologiques associés à ces immunodéficiences et je caractérise les défauts biochimiques de la signalisation TCR:CD3:ζ associés à ces déficits. Enfin, je compare mes observations avec les modèles murins déficients Lck-/-, Zap-70-/- et Itk-/- déjà bien établis. / T lymphocytes express either a preTCR, or a clonotypic γδ TCR or αβ TCR together with the CD3-complex and the associated ζ-chain. TCR:CD3:ζ-signalling is crucial for T cell development and antigen-specific activation including proliferation, differentiation, effector functions and apoptosis of mature T cells. Protein tyrosine kinase (PTK) cascades lie at the heart of proximal TCR:CD3:ζ-signalling. The CSK-, SRC-, SYK- and TEC-family members C-terminal SRC kinase (CSK), lymphocyte-specific protein tyrosine kinase (LCK), ζ-chain associated protein tyrosine kinase of 70 kDa (ZAP-70) and interleukin-2-inducible T cell kinase (ITK), respectively, are the major T cell players. After TCR:CD3:ζ-complex triggering, activation of PTKs results in tyrosine phosphorylation signals. These include phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) of the CD3 and ζ-chains, and adaptor proteins that nucleate the proximal LAT:SLP-76-signalosome controlling almost all TCR:CD3:ζ-induced signalling events. These events initiate Ca2+-flux, activation of mitogen-activated protein kinases (MAPKs), activation of nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB), activation of nuclear factor of activated T cells (NFAT) and activator protein 1 (AP-1) as well as actin reorganization, cell-adhesion and motility. Throughout the last five decades, the immune system has been extensively investigated in vitro and in animal models such as the murine system. Additionally, studying and taking care of human primary immunodeficiency diseases (PIDs) has been seminal for our understanding of the human immune system as animal models not always recapitulate the subtleties found in men. In my doctoral thesis I report the first case of autosomal recessive human LCK-deficiency, a novel autosomal recessive mutation leading to human ZAP-70-deficiency and a novel autosomal recessive mutation leading to human ITK-deficiency. I provide detailed clinical, immunological and biochemical analyses especially of TCR:CD3:ζ-signalling and compare my findings to the well-established Lck-/-, Zap-70-/- and Itk-/- murine models.

Le LHC entrera dans sa phase à haute luminosité vers 2027 et pour profiter de l’augmentation importante du taux de collisions, ATLAS, et plus particulièrement son trajectographe doivent être améliorés en terme de résistance aux radiations et traitement de données à un taux accru. Grace au nouveau design du trajectographe at à l’amélioration d’algorithmes d’étiquetage des saveurs de jets, l’identification de jets issus de la désintégration de B hadrons sera facilitée et des canaux de physique possédant des quarks b dans leurs états finaux seront plus facilement accessible, parmi lesquels le couplage trilinéaire du boson de Higgs. La résistance aux raditions des capteurs à pixels en silicium joue un rôle primordial dans leur utilisation auprès des experience LHC. La quantification de l’impact des rayonnements sur les capteurs silicium est un enjeu crucial : un outil de digitisation des dommages des rayonnements a été développé pour modéliser l’impact des radiations dans les simulations Monte Carlo d’ATLAS. Le test de capteurs à pixels planaires, développés par le LPNHE et la fonderie FBK, constitue la partie principale de cette thèse. Les trois productions de capteurs testées possèdent plusieurs designs technologiques. Pour maximiser l’acceptance géométrique du détecteur, des capteurs à bord mince ont été développés. Deux options de polarisation durant les phases de test ont ausssi été étudiée. Les capteurs ont été testés à plusieurs phases d’irradiation. L’optimisation d’algorithme de b-tagging basé sur la reconstruction de vertex secondaire sera aussi présentée, ainsi qu’une étude concernant les performances du b-tagging à haut pT . / By 2027, the LHC will enter its high luminosity regime, providing protons protons collisions at an unprecedented rate. The LHC experiments whill have to be upgraded to cope with this higher data rate. The new ATLAS Inner Tracker (ITk) will allow a better identification of b-quarks and interesting physics signature with b-quarks in the final states such as the Higgs trilinear coupling will be reachable. The work performed during this thesis consisted in testing planar pixel sensors for the ITk, as well as optimizing b-tagging algorithms. In parallel, a study on the radiation damage on silicon pixel sensors have been performed. The radiation hardness of silicon sensors plays a determinant role as it allows them to be efficient in the highly radiative environment at LHC. Understanding the impact of radiation in silicon sensors is a major challenge and a radiation damage digitizer which models radiation damage effects in ATLAS Monte Carlo simulations is currently developed by the ATLAS experiment. Three ITk silicon planar pixel sensors productions of LPNHE and FBK have been developed, produced and tested on beam. Sensors from these three productions aim to be part of the ITk and have to demonstrate good performance after being irradiated at high fluences. Several technological designs have been investigated, such as temporary metal biasing option and active edges which maximize the geometrical acceptance of the sensors. The optimization of b-tagging SV1 algorithm (a secondary-vertex based algorithm) will be pre- sented as well as a study on the extrapolation of b-tagging performances at high pT.

The strength of peptide:MHC interactions with the T cell receptor (TCR) is correlated with the time to first cell division, the relative scale of the effector cell response, and the graded expression of activation-induced proteins. The TCR proximal tyrosine kinase ITK simultaneously influences many biochemically separate signaling cascades. T cells lacking ITK exhibit selective impairments in effector T cell responses after activation, but under the strongest signaling conditions ITK activity is dispensable. To gain insight into whether TCR signal strength and ITK activity tune observed graded gene expression through unequal activation of disparate signaling pathways, I examined NFAT, NF-κB and MAP kinase pathways during early activation of individual naïve OT-I CD8+ T cells using peptide-loaded antigen presenting cells. Utilizing both measurement of transcription factor translocation in single T cell nuclei and conventional phospho-flow cytometry, I observed digital activation of Erk-MAPK and NFAT1 at all peptide doses and avidities. However, NF-κB activation showed a graded response to variation in TCR signal strength and was more sensitive to treatment with an ITK inhibitor. Inhibitor-treated cells showed poor induction of AP-1 factors Fos and Fosb, NF-κB response gene transcripts, and survival factor Il2 transcripts. ATAC-seq analysis revealed genomic regions most sensitive to ITK inhibition are enriched for NF-κB and AP-1 motifs. Together, these data indicate a key role for ITK in orchestrating optimal activation of separate TCR downstream pathways, specifically aiding NF-κB activation. More broadly, I describe a mechanism by which variation in TCR signal strength can produce patterns of graded gene expression in activated T cells.